Urea derivatives of 2-imidazolidone

ABSTRACT

Ureas of the structure   WHEREIN X if F or OCH3; Y is O or NH; m is 0, 1 or 2, and N AND N&#39;&#39; EACH ARE 0 OR 1 ARE USEFUL IN PREVENTION OF OZONE DAMAGE TO PLANTS.

United States Patent 1191- Wat [ Jan.7,1975

l l UREA DERTIVATKVES 0F Z-lIMlDAZOLIDONE [52] U.S. Cl 260/309.7, 71/88, 71/92,

260/244 R, 260/2564 C, 260/307 C, 260/3097 [51] Int. Cl C07d 47/34 [58] Field of Search 260/3097 [56] References Cited UNlTED STATES PATENTS 8/l950 Wilson 260/309] OTHER PUBLICATIONS Beyer et 211., Chem. Ber., Vol. 97, pages l,031l,036,

(1964), Q 1.134. Rabinowitz et al, J. Org. Chem., Vol. 34, pages 372-376, (1969), QD241J6.

Primary Examiner-Natalie T rousof [57] ABSTRACT Ureas of the structure m is 0, l or 2, and n and n each are 0 or I are useful in prevention of ozone damage to plants.

3 Claims, N0 Drawings 3 ,85 9 ,3 l 1 I 2 UREA Z-IMI DA Z OLI DONE The new compounds include those having the follow- BACKGROUND OF THE INVENTION mg f 1. Field of the Invention 1 Certain heterocyclic ureas are useful in protecting 5 plants from the deleterious effects of atmospheric ozone. Ozone is a common air pollutant around urban K) areas which has been found to damage crop plants, ornamental plants and shade and forest trees. Polluted air 0 is estimated to cost farmers a half-billion dollars a year. H Even air that contains a level of ozone below that com- C6H4 OCH3 NHCONmCHtCHD-N 0 mon to urban areas reduces yields of many crops.

2. Description of the Prior Art 0 Ureas have been widely employed for selective biological activity. Some have been suggested for pharmal5 C6H5NHCONH N/ cological uses, e.g. Shoeb, et al., [C.A. 68, 12946e (1968)] propose l-phenyl-3-(Z-pyridylethyl) ureas to lower blood sugar. Others such as 0 (13H: CuHsNHCONHCHzCHzN NH NN C6H5NHCONH v. V A, V i

i.e., 5-(3-phenylureido)-1,3-dimethylpyrazole, have CHNHCONH N CH5NHCONHCHCH N been found effective as plant defoliants in U.S. Pat. No. i i i i 3,646,059. l-Morpholino-3-phenylurea has been shown to have cytokinin activity in a cellular assay [Bruce, Proc. Roy. Soc (London) Ser. B 165 (1966) SPECIF 1C EMBODIMENTS OF THE NVENT'ON 245 2651. Many have found application as herbicides, the following illustrative examples Parts are y but none have been reported to be useful in protecting Weight unless Otherwise Statedplants against atmospheric ozone. EXAMPLE 1 DESCRIPTION OF THE INVENTION l-[2-(2-Oxol-imidazolidinyl)ethyl]-3-phenylurea The ureas of this invention have the general structure m 0" n 1, n 0, p Y NH X...) NfiCONHwH CHfir-N (Y) O H H CH5NC0 HEN 94) benzene V l where CBH5NHUNH X is F or OCH N Nll. Y is O or NH,

m is 0-2 and nand n'are0or l. I The new Compounds are usually Obtained y action To a mixture of 6.5 g of commercially available l-(2- of phenylisocyanate or a monoor di-fluoroor meaminoethyl)-2'imidazolidone and ml benzene was thoxy-substituted phenyl isocyanate with aheterocyclic added 5.5 ml of phenyl isocyanate. The strongly amino compound of the structure thermic reaction was moderated by cooling to 25. The mixture was stirred at 25 for 4 hr. It was cooled in ice and the mixture was filtered. The solid product was crystallized from 250 ml of acetone to give 6.8 g of white 1-[2-(2-oxo-1-imidagolidinyl)ethyl]-3- HQMCHZCHDDFN/ B phenylurea, mp l62-l64.

H2 H2 lR(Nu ol) 3.1 u (NH); 5.9 (C=O) g NMR(DMSO-d m(lH) 8.45 '6 (ArNH); m(5H) (C 6.7-7.5 (aromatic H); m(2H) 5.9-6.3 (NH); m(8H) mflmw 3.0-3.5 (CH 65 A second crop, 1.5 g, mp l60-l63 brought the total where Y is NH or 0. yield to 8.3 g (67% yield). This reaction is generally rapid and should be so con- Increased yields were obtained when the starting ducted as to avoid local overheating. imidazolidone (Aldrich technical grade) was purified -hr at 25, concentrated at reduced pressure. Hexane EXAMPLE 2 1-(Tetrahydro-2-oxo-l,3-oxazin-3-yl)-3-phenylurea 3 0 tpl- 3-Hydrazino-l-propanol The procedure of G. Gever, J. Am. Chem. Soc. 76,

1283 (1954) was used.,A mixture of 40 g of sodium hydroxide in 250 g of hydrazine hydrate was heated to 95. The heat source was removed and 94 g of 3- chloropropanol was added at a rate necessary to maintain an internal temperature of 95-l00. The mixture was concentrated at reduced pressure, filtered, and the solids were washed with ethanol. The filtrate was distilled through a 6-in. Vigreux column to give 49.6 g of 3-hydrazino-1-propanol as a colorless liquid, bp 9l95 (0.2-0.5 mm) (reported bp l02104 (0.6 mm)).

1R(film) 3.1 u (NH, OH)

NMR(CDCl m(4H) 3.9 8 (NH, OH); t(2H) 3.70, J 6 (CH O);

t(2H) 2.92,] 6 (CH N H2)- Step 2 3-Amino-tetrahydro-1,3-oxazin-2-one quintet (2H) 1.72, J 6

The procedure of K. Hayes, J. Am. Chem. Soc. 77, 2333 (1955) was used. A solution of sodium methoxide was prepared from 1.5 g of sodium in ml of methanol. A portion (4 ml) of this reagent was added to a mixture of 18.0 g of the 3-hydrazinopropanol and 31 g of diethyl carbonate. The mixture was refluxed for 2 hr while the alcohol formed was removed by distillation. The product was distilled at reduced pressure to give 10.4 g of 3-amino-tetrahydro-1,3-oxazin-2-one as a colorless liquid, bp 105 (0.5 mm) 45% yield.

1R(film) 3.0 p. (NH); 5.9 (C=O) NMR(CDCl m(4H) 4.0-4.5 8 (Cl-1 0, NH t(2H) 3.51, J 6 (CH N); m(2H) 2.10 (CH Step 3 l'(Tetrahydro-2-oxo-l,3-oxazin-3-yl)-3- phenylurea To a mixture of 5.4 g of 3-amino-tetrahydro-l,3- oxazine-Z-one and 50 ml glyme was added 5.0 ml of phenyl isocyanate. After an exothermic reaction a white solid formed. The mixture was refluxed for 1 hr; cooled; diluted-with hexane and filtered. The solid product was crystallized from 200 ml of ethanol to give 5.8 g (53% yield) of white cotton-like needles of 1- (tetrahydro-2-oxo-1,3-oxazin-3-yl)-3-phenylurea, mp 204-207.

IR(Nujol) 3.0 p. (NH); 6.0, 5.85 (C=O) NMR(DMSO-d m(lH) 8.80 8 (NH); m(lH) 8.30 (NH); m(SH) 6.8-7.6 (aromatic H); t(2H) 4.20, J 5 (CH O); t(2H) 3.50, J 6.5 (CH N); m(2H) 2.0 2)- An improved synthesis of the latter compound resulted after removal of the alcohol produced in Step 2, the residue was evacuated at 150 (0.5 mm). After cooling the slush, 300 ml of glyme was added and the mixture filtered. Concentration of the filtrate gave crude amine as a yellow oil which was not further purified. It was treated with phenyl isocyanate as in Step 3 to give a 51% overall yield (2 steps) of the urea, mp 201-203.

Calcd for C11H13N3O3:

C, 56.16; H, 5.57; N, 17.86 Found:

. C, 55.95; H, 5.24; N, 17.64

EXAMPLE 3 l-(2-Oxo-l-imidazolidinyl)-3-phenylurea l-Amino-2-imidazolidinone The general procedure of J. G. Michels and G. Gever, J. Am. Chem. Soc., 78, 5349 (1956) was used. To a solution of 63 g of 2-imidazolidinone in 2 l. of 2N sulfuric acid was added 50.5 g of sodium nitrite in small portions over a period of 13 min. with external cooling to maintain an internal temperature of 36. The mixture was stirred at 0 for 1.5 hr. Zinc dust g) was added over a 1 hr period below 20. The excess zinc was removed by filtration and solid barium hydroxide was added to the filtrate until a pH of 6 was attained. The white solid was removed by filtration. Aqueous (50%) sodium hydroxide was added to the filtrate until a pH of 7.9 was attained and the solid was removed by filtration. The filtrate was concentrated at reduced pressure. Methanol was added and the precipitated salts were removed by filtration. Concentration of the filtrate gave an oil which was dissolved in chloroform and'dried over sodium sulfate. Upon removal of the solvent, a white solid remained which was crystallized from 25 ml of chloroform to give 5.6 g large white prisms of l-amino-2-imidazolidinone, mp 99-l IR(Nujol) 3.1 u (NH); 5.9 (C=O).

NMR(DMSO) m(lH) 6.42 5 (NH); m(2H) 4.12 (NHQ); m(4H) 3.21 (CH Step 2 l-(Z-Oxo-l-imidazolidinyl)-3-phenylurea To a mixture of 3.0 g of 1-amino-2-imidazolidinone in 30 ml glyme was added 3.3 ml of phenyl isocyanate, resulting in an exothermic reaction and formation of a white solid. After 30 min. at 25, 30 ml of hexane was added and the mixture filtered. The solids were washed well with hexane, suspended in hot ethanol, cooled, and filtered to yield 5.9 g of white solid l-(2-oxo-limidazolidinyl)-3-phenylurea, mp 235-238.

lR(Nujo1)- 3.0 ,u. (NH); 5.80, 5.92 (C=O).

NMR(DMSO) m(lH) 8.75 8, m(lH) 8.07, m(lH) 6.86 (NH); m(SH) 7.0-7.7 (aromatic H); m(4H) 3.2-3.6 (CH EXAMPLE 4 l-(2-Ox0-3-oxazolidinyl)-3-phenylurea Y 0 Step 1 3-Amino-2-oxazolidone 2Hs =O NaOCH:

0 tLN-: o

The procedure used was the same as that in Step 2 of Example 2 except Z-hydrazinoethanol was used. The crude product was a solid and could be crystallized from chloroform to give large white needles, mp 66-68. lR (Nujol) 3.0 [1. (NH); 5.7 (C=O). NMR (CDCl;.)- m(2H) 4.16-4.50 6 (CH O); m(l-2H) 4.09 (NHZ); m(2H) 3.50-3.88 (CH N).

Step 2 l-(2-Oxo-3-oxazolidinyl)-3-phenylurea To a mixture of 6.0 g of 3-amino-2-oxazolidone in 60 ml of glyme was added 6.6 ml of phenyl isocyanate, resulting in an exothermic reaction and formation of a white solid. The mixture was refluxed for min., cooled, and filtered. The solid product was crystallized from acetone to give 3.6 g of white crystals, mp 185l90. lR(Nujol) 3.11 M (NH); 5.70 (C=O); 5.95 (C=O). NMR(DMSO) m(lH) 8.97 6, m(lH) 8.35 (NH); m(SH) 6.9-7.7 (aromatic H); m(2H) 4.2-4.6

5 (CH O); m(2H) 3.5-3.9 (CH N).

LII

EXAMPLE 5 1-(Tetrahydro-2-oxo-1,3-oxazin-3-yl)-3-(2- fluorophenyl)urea Step 3 of Example 2 was repeated using 2- fluorophenyl isocyanate. The product was cryst. from acetone to give white needles, mp -l93. Spectra were similar to that in Example 2.

Using the general procedure of the preceding example with 4-fluorophenyl isocyanate, this isomer was prepared, mp 2l6-2l9.

EXAMPLE 7 1-(Tetrahydro-2-oxo-l,3-oxazin-3-yl)-3-(3- fluorophenyl)urea When 3-fluorophenyl isocyanate was used in the procedure of Example 6, the 3-isomer was prepared, mp l99-203.

EXAMPLE 8 l-(2-Tetrahydro-2-oxo-l,3-oxazin-3-yl)-3-(2,4-dime- I thoxyphenyUurea The above compound was similarly prepared using 2,4-dimethoxyphenyl isocyanate. The solid product was cryst. from glyme, mp l83-l90.

When 3-chloropropanol is reacted with l-(2-aminoethyl)-3-phenylurea and the resulting 1-[2-(3-hydroxypropylamino)ethyll-3-phenylurea is reacted with diethyl carbonate according to the general processes of steps 1 and 2 of Example 2, there is obtained 1-[2- (tetrahydro-Z-oxo-1,3-oxazin-3-yl)ethyl]-3- phenylurea.

Repetition of the general process of Example 1 except using a fluorophenyl isocyanate (Examples 5-7) or 2,4-dimethoxyphenyl isocyanate (Example 8) gives the corresponding fluoroor methoxyphenyl-Z-(Z-oxol-imidazolidinyl)ethylureas. Reaction of 1 -amino-2- imidazolidinone (see Example3) with the above substituted isocyanates gives the corresponding fluoroor methoxyphenyl 2-oxo-l imidazolidinylureas. lsomeric difluorophenyl and methoxyphenyl isocyanates can be substituted for phenyl or substituted phenyl isocyanates in the preceding examples to give 3-difluorophenyl and 3-methoxyphenyl 1-(2-oxotetrahy dro-l,3-oxazin-3- yl)ureas, l-(-2-oxo-l-imidazolidin-yl) ureas, l-(2-oxol-tetrahydro-oxazinyl)ureas and 1-(2-oxo-ltetrahydropyrimidinyl) ureas. v

The compounds of the invention are useful to protect plants against the harmful effects of ozone. The amount of compound required for optimum effects will depend on the particular crop and environment under which it is growing. Within the meaning of this case, the amount of compound necessary to accomplish protection against ozone will be termed an effective amount. Normally, the rate at which the compound is applied will range from 0.02 to 3.0 kilogram per hectare although higher rates can be used. One skilled in the art will be able to select the appropriate rate of application for any particular situation. Plants that can be protected from the deleterious effects of ozone include oranges, lemons, tobacco, grapes, potatoes, tomatoes, soybeans, corn, lettuce, alfalfa and ornamental plants.

The compounds of the present invention can be used in the form of compositions which are prepared by admixing at least one of the active compounds with an inert diluent, such as pest control adjuvants or modifiers, to provide compositions in the form of dusts, water-dispersible powders, high-strength concentrates, and aqueous or organic dispersions. Thus, the compounds of this invention can be used with a carrier or diluent agent such as a finely divided solid, an organic liquid, water, a wetting agent, a dispersing agent, an emulsifying agent, or any suitable combination of these.

The compositions, especially liquids and wettable powders, may contain as a conditioning agent one or more surface-active agents, sometimes called surfactants, in amounts sufficient to render a given composition containing the compounds of this invention readily dispersible in water or in oil.

The following examples illustrate the use of the above compounds to.inhibit ozone damage to plants.

EXAMPLE A Pinto beans (Phaseolus vulgaris) were grown in vermiculite in 4-in. plastic pots under 12-hr days with 2,200 foot-candles illumination (fluorescent plus incandescent). The daytime temperature and relative humidity were F. and 75%, respectively. At night they were 65F. and Thirteen days after planting a representative plant was sprayed with a 500 ppm solution of l-(tetrahydro-Z-oxo-l,3-oxazin-3-yl)-3-phenylurea (Ex. 2). The spraying solution also contained 3.5% glycerol and 175 ppm of an alkyl polyethylene oxide surface-active agent (Tergitol l5-S-l2). Two other plants were sprayed with the glycerol-surface active agent solution without the compound and two additional plants were not sprayed.

On the following day, these plants were exposed to 60 pphm (parts per hundred million) 0 for 2-% hr in a fumigation chamber having about one air change a minute. Two days later the five plants were examined. The ozone had caused extensive damage to the two primary leaves of the unprotected plants. Damage consisted of brown lesions and bifacial tissue collapse. In the two unsprayed plants the damaged area made up and of the leaf area respectively. The plants sprayed with glycerol and surface active agent only were damaged to the extent of 80% and 85% of the leaf surface. The plant treated with the heterocyclic urea suffered no visible damage. This plant returned to the fumigation chamber and again exposed to 60 pphm ozone for 2-% hr. When the plant was examined two days later there was still no visible damage. A frest unsprayed control plant, which was fumigated along with the test plant, was damaged to the extent of 80% of its leaf area.

EXAMPLE B EXAMPLE C The general procedure of ExampleA was repeated except a 500 ppm solution. of l-(2-oxo-limidazolidinyl)-3-phenylurea (Ex. 3) was sprayed on the plant 24hr prior to fumigation. Two days after fumigation there was no visible injury. The plant was refumigated and after two more days was again inspected. No damage was observed.

EXAMPLE D The procedure of Example A was followed exceptthat a 500 ppm solution of 1-(tetrahydro-2-oxo-1,3- oxazin-3-yl) 3-(2-fluorophenyl)urea (Ex. 5) was sprayed on the plant before fumigation. Two days after fumigation there was no observable damage. The plant was refumigated. Two days later the visible damage was only of the leaf surface.

EXAMPLE E The procedure of Example A was followed except that a 5&0 ppm solution of l-(tetrahydro-2-oxo-1,3- oxazin-B-yl)-3-(3-fluorophenyl)urea (Ex. 7) was sprayed on the plant before fumigation. Two days after fumigation the foliar damage was 10%. The plant was refumigated. Two days later only of the leaf area was damaged.

EXAMPLE F The procedure of Example A was followed except that a 500 ppm solution of l-(tetrahydro-2-oxo-l,3- oxazin-3-yl)-3-(4-fluorophenyl)urea '(Ex. 6) was used. Two days after fumigation there was no visible damage. The plant was refumigated. Two days later the foliar damage was only 15%.

EXAMPLE G compounds of Examples A and B give good protection when applied at concentrations of 50 ppm. For foliar applications, it is preferred that a conventional wetting agent be present, e.g.'50500 ppm of a nonionic detergent to aid in uniform coverage.

In place of foliar application, the compounds can be applied to soil for absorption through the roots. The latter may provide effectiveness over a greater length of time than generally effective as a foliar spray. Foliar applications are preferred to be within a week before exposure to atmosphere containing a substantial amount of ozone.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

l. A compound of the formula 2. The compound of claim 1 wherein m O, n l, and Y NH; 1-[2-(2-oxo1-imidazolidinyl)ethyl]3- phenylurea.

3. The compound of claim 1 wherein m n O, and Y NH; l-(2-oxo-l-imidazolidinyl)-3-phenylurea. 

1. A COMPOUND OF THE FORMULA
 2. The compound of claim 1 wherein m O, n 1, and Y NH; 1-(2-(2-oxo-1-imidazolidinyl)ethyl) -3-phenylurea.
 3. The compound of claim 1 wherein m n O, and Y NH; 1-(2-oxo-1-imidazolidinyl)-3-phenylurea. 